Publications by authors named "Weihua Gao"

108 Publications

IFI16 directly senses viral RNA and enhances RIG-I transcription and activation to restrict influenza virus infection.

Nat Microbiol 2021 May 13. Epub 2021 May 13.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, China.

The retinoic acid-inducible gene I (RIG-I) receptor senses cytoplasmic viral RNA and activates type I interferons (IFN-I) and downstream antiviral immune responses. How RIG-I binds to viral RNA and how its activation is regulated remains unclear. Here, using IFI16 knockout cells and p204-deficient mice, we demonstrate that the DNA sensor IFI16 enhances IFN-I production to inhibit influenza A virus (IAV) replication. IFI16 positively upregulates RIG-I transcription through direct binding to and recruitment of RNA polymerase II to the RIG-I promoter. IFI16 also binds to influenza viral RNA via its HINa domain and to RIG-I protein with its PYRIN domain, thus promoting IAV-induced K63-linked polyubiquitination and RIG-I activation. Our work demonstrates that IFI16 is a positive regulator of RIG-I signalling during influenza virus infection, highlighting its role in the RIG-I-like-receptor-mediated innate immune response to IAV and other RNA viruses, and suggesting its possible exploitation to modulate the antiviral response.
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http://dx.doi.org/10.1038/s41564-021-00907-xDOI Listing
May 2021

The Multifaceted Regulation of Mitochondria in Ferroptosis.

Life (Basel) 2021 Mar 10;11(3). Epub 2021 Mar 10.

State Key Laboratory of Agricultural Microbiology, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Ferroptosis is characterized as a novel form of regulated cell death, which is initiated by the lethal accumulation of lipid peroxidation catalyzed by cellular labile free iron. This iron driven cell death sharply differs from other well characterized forms of regulated cell death at morphological, genetic and biochemical levels. Increasing research has elaborated a high relevance between dysregulated ferroptosis and the pathogenesis of degenerative diseases and organs injury in human patients. Additionally, targeted induction of ferroptosis is considered as a potentially therapeutic design for the clinical intervention of other therapy-resistant cancers. It is well understood that mitochondria, the cellular powerhouse, determine several types of regulated cell death. Recently, compromised mitochondrial morphology and functionalities have been primarily formulated in ferroptosis. Several mitochondria associated proteins and metabolic processes have been elaborated to fine-tune ferroptotic program. Herein, we critically review the recent advances in this booming field, with focus on summarizing the multifaceted mitochondrial regulation of ferroptosis and providing a perspective on the potential biochemical basis. Finally, we are attempting to shed light on an integrative view on the possibility of mitochondria- and ferroptosis-targeting therapeutics as novel treatment designs for the intervention of ferroptosis related diseases.
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http://dx.doi.org/10.3390/life11030222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001967PMC
March 2021

Creatine improves the flesh quality of Pacific white shrimp (Litopenaeus vannamei) reared in freshwater.

Food Chem 2021 Aug 8;354:129498. Epub 2021 Mar 8.

Key Laboratory of Freshwater Biodiversity Conservation, Ministry of Agriculture, Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan 430223, China. Electronic address:

Creatine improves flesh quality on mammalian but studies on crustaceans are scarce. In the present study, diets with six levels of creatine (1.23, 2.58, 5.12, 8.28, 14.12, 24.49 g kg diet) were hand-fed to juvenile Litopenaeus vannamei (IBW: 1.50 ± 0.02 g) reared in freshwater for 46 days. Results showed creatine supplementation did not affect the growth performance (FBW: 17.04 ± 1.28 g) or the content of guanidinoacetic acid in muscle and hepatopancreas whereas significantly increased muscular creatine content. Diet with 8.28 g kg creatine significantly increased muscular hardness and chewiness by decreasing myofiber diameter and increasing myofiber density. Additionally, creatine downregulated the mRNA expression of fast sMyHC1, sMyHC2, sMyHC6a and upregulated slow sMyHC5 and sMyHC15 mRNA expression. Muscular protein, collagen, total amino acid and flavor amino acid contents increased with creatine supplementation. In conclusion, the diet with 8.28 g kg creatine improved the flesh quality of L. vannamei.
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http://dx.doi.org/10.1016/j.foodchem.2021.129498DOI Listing
August 2021

Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.

J Virol 2021 Mar 17. Epub 2021 Mar 17.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.Avian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.
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http://dx.doi.org/10.1128/JVI.01578-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139711PMC
March 2021

Dual-Modal Immunosensor with Functionalized Gold Nanoparticles for Ultrasensitive Detection of Chloroacetamide Herbicides.

ACS Appl Mater Interfaces 2021 Feb 29;13(5):6091-6098. Epub 2021 Jan 29.

Key Laboratory of Zoonoses Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.

Convenient and ultrasensitive detection of pesticides is demanded for healthcare and environmental monitoring, which can be realized with a dual-modal strategy. In this paper, based on a biotin-labeled IgG-modified gold nanoparticle ([email protected]) probe, a dual-modal immunosensor was proposed for detecting chloroacetamide herbicides. This platform is relied on the dephosphorylation of ascorbic acid 2-phosphate (AA2P) by alkaline phosphatase (ALP). In addition to this process, ascorbic acid (AA)-triggered deposition of silver on gold nanostars (AuNSs) and the fluorogenic reaction of dehydrogenated AA and -phenylenediamine (OPD) occur sequentially. Thus, the dual readout of the color change of red-green-blue (RGB) and fluorescence generation in situ induced by crystal growth can be used. The limits of detection (LODs) were as low as 1.20 ng/mL of acetochlor (ATC), 0.89 ng/mL of metolachlor, 1.22 ng/mL of propisochlor, and 0.99 ng/mL of their mixture by a smartphone and 0.44 ng/mL of ATC, 1.59 ng/mL of metolachlor, 2.80 ng/mL of propisochlor, and 0.72 ng/mL of their mixture by a spectrofluorometer. The recoveries from corn were 91.4-105.1% of the colorimetric mode and 92.4-106.2% of the fluorescent mode. Due to its simple observation mode and good performance, this dual-modal immunosensor possesses considerable application prospects.
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http://dx.doi.org/10.1021/acsami.0c21760DOI Listing
February 2021

Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study.

Nat Commun 2020 10 6;11(1):5009. Epub 2020 Oct 6.

Clinical Pharmacology Unit, Zealand University Hospital, Køge, Denmark.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.
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http://dx.doi.org/10.1038/s41467-020-18849-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538555PMC
October 2020

Facile synthesis of biocompatible L-cysteine-modified MoS nanospheres with high photothermal conversion efficiency for photothermal therapy of tumor.

Mater Sci Eng C Mater Biol Appl 2020 Dec 7;117:111371. Epub 2020 Aug 7.

School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China. Electronic address:

Photothermal therapy (PTT) can take advantage of the photothermal effects of photothermal agents to acquire the energy from laser irradiation and convert it into heat. This can intensively elevate the temperature of the surrounding environment to directly destroy the cancer cells. It is expected that PAs with strong absorption in near infrared (NIR) range might possess the ideal tissue-transparent feature and minimal damage to surrounding healthy tissues, beneficial to the practical application. Herein, well-dispersed L-cysteine modified MoS (MoS-Cys) nanospheres with the average diameter of about 422 nm and strong NIR adsorption were successfully synthesized through a facile method. The as-prepared MoS-Cys nanospheres are composed of nanosheets with the average thickness of about 13.7 nm. The photothermal conversion efficiency of the as-prepared MoS-Cys nanospheres with the very low concentration of 50 μg/mL was determined to be 35% when exposed to 808 NIR laser at the power density of 0.8 W/cm, much higher than those of the previous reports with same dose and power density. MoS-Cys nanospheres possessed the good photothermal ablation effect to significantly inhibit the growth of tumor in vivo. Furthermore, MoS-Cys nanospheres did not exhibit detectable side effects, suggesting their good in vitro and in vivo biocompatibility.
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http://dx.doi.org/10.1016/j.msec.2020.111371DOI Listing
December 2020

Swine MicroRNAs and Restrict the Cross-Species Infection of Avian Influenza Virus.

J Virol 2020 11 9;94(23). Epub 2020 Nov 9.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China

Avian influenza virus (AIV) can cross species barriers to infect humans and other mammals. However, these species-cross transmissions are most often dead-end infections due to host restriction. Current research about host restriction focuses mainly on the barriers of cell membrane, nuclear envelope, and host proteins; whether microRNAs (miRNAs) play a role in host restriction is largely unknown. In this study, we used porcine alveolar macrophage (PAM) cells as a model to elucidate the role of miRNAs in host range restriction. During AIV infection, 40 dysregulation expressed miRNAs were selected in PAM cells. Among them, two (; swine) miRNAs, and , could inhibit the infection and replication of AIV in PAM cells by directly targeting viral genome and inducing cell apoptosis via inhibiting the expression of anti-apoptotic protein HMBOX1. Avian but not swine influenza virus caused upregulated expressions of and in PAM cells. We further found that NF-κB P65 was more effectively phosphorylated upon AIV infection and that P65 functioned as a transcription activator to regulate the AIV-induced expression of Importantly, we found that and could also be specifically upregulated upon AIV infection in newborn pig tracheal epithelial (NPTr) cells and also exerted anti-AIV function. In summary, our study indicated that miRNAs act as a host barrier during cross-species infection of influenza A virus. The host range of an influenza A virus is determined by species-specific interactions between virus and host cell factors. Host miRNAs can regulate influenza A virus replication; however, the role of miRNAs in host species specificity is unclear. Here, we show that the induced expression of and in swine cells is modulated by NF-κB P65 phosphorylation in response to AIV infection but not swine influenza virus infection. and exerted antiviral function via targeting viral RNAs and causing apoptosis by inhibiting the expression of HMBOX1 in host cells. These findings uncover miRNAs as a host range restriction factor that limits cross-species infection of influenza A virus.
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http://dx.doi.org/10.1128/JVI.01700-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654260PMC
November 2020

[Preliminary study of medialization thyroplasty for unilateral vocal fold immobility].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Mar;34(3):218-222;226

Department of Otorhinolaryngology Head and Neck Surgery,Beijing University First Hospital,Beijing,100034,China.

To explore the feasibility and effectiveness of medialization thyroplasty for the treatment of unilateral vocal fold immobility (UVFI). Eight UVFI patients were performed medialization thyroplasty under local anesthesia. We made a window in the thyroid cartilage under local anesthesia, then insert the preformed silicone implant. The paralyzed vocal fold was medialized to make the glottis closed. Fibrolaryngoscope video recording, subjective voice analysis and CT thin slice scan of larynx were done before and after surgery to evaluate closure of vocal cords, improvement of voice and position of implantation. The preoperative and postoperative voice handicap index 30(VHI-30) of the 8 patients were 91.5(64.5, 97.5) and 22.5(5.0, 47.5) respectively, which showed statistical difference(<0.05). GRBAS results: The postoperative G, R, B, A were all smaller than preoperative ones, which showed statistical difference(<0.05); the pre and postoperative S was both 0. The fibrolaryhgoscope recording showed the preoperative and postoperative score of incomplete glottis closure was 1.0(1.0, 1.0) and 4.0(2.5, 5.0) respectively, which showed statistical difference(<0.05). Postoperative laryngeal CT showed significant vocal cord medialization on the affected side. Aspiration was significantly improved in 4 patients who were suffered from this symptom before the surgery. No complication occurred with the 8 patients during 5 to 48 months follow up. Medialization thyroplasty can effectively improve vocalization and quality of life in patients with UVFI.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.03.008DOI Listing
March 2020

An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza.

medRxiv 2020 Apr 25. Epub 2020 Apr 25.

Science Policy and Research, National Institute for Health and Care Excellence, UK.

Background: To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza.

Methods: We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014-19.

Results: 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use.

Conclusions: Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.
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http://dx.doi.org/10.1101/2020.04.22.20074336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239064PMC
April 2020

A D200N hemagglutinin substitution contributes to antigenic changes and increased replication of avian H9N2 influenza virus.

Vet Microbiol 2020 Jun 30;245:108669. Epub 2020 Apr 30.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China. Electronic address:

Influenza virus hemagglutinin (HA) plays an important role in viral antigenicity, replication and host range. However, few amino acid positions in HA were reported to play multiple functions in both viral antigenicity and replication. In the present study, through analyzing the amino acid sequences of H9N2 avian influenza viruses (AIVs) isolated from China, we identified a multi-functional substitution of D200N in HA1 protein. Firstly, the substitution of D200N changed the antigenicity of H9N2 AIVs. Secondly, the D200N increased the HA cleavage efficiency and reduced acid and thermal stability of HA protein, which triggered viral-endosomal membrane fusion whereby promoted the release of viral genome into the host cytoplasm. Finally, residue 200-N increased the replication of H9N2 viruses in both chicken embryo fibroblast (CEF) cells and chicken embryonated eggs. In summary, the D200N substitution is a newly identified antigenicity and replication determinant of H9N2 AIVs, which should be paid more attention during surveillance.
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http://dx.doi.org/10.1016/j.vetmic.2020.108669DOI Listing
June 2020

Tolerability, Efficacy and Feasibility of Concurrent Gemcitabine and Cisplatin (CGP) Combined With Intensity Modulated Radiotherapy for Loco-Regionally Advanced Carcinoma of the Cervix.

J Cancer 2020 19;11(9):2632-2638. Epub 2020 Feb 19.

Department of Haematology, Zhengzhou University People's Hospital & Henan Provincial People's Hospital 450003, China.

Gemcitabine and cisplatin combined with conventional radiotherapy in treating patients with cervical cancer, resulted in a favourable conclusion but accompanied with high toxicity. The objective of our research was to assess the tolerability, efficacy and feasibility of dual chemotherapy in addition to image-guided adaptive brachytherapy and highly conformal external beam radiation therapy. From June 2011 to November 2013, 81 cervical cancer patients with FIGO stage IB2-IIIB medical records were retrospectively reviewed. All patients received whole pelvic radiotherapy (WPRT) to a total dose of 50.4 Gy/ 1.8 Gy Chemoradiotherapy prescription objectives were: concurrent gemcitabine (125 mg/m) and cisplatin (30 mg/m) during the 6 weeks of external beam radiation therapy (EBRT) followed by two cycles of gemcitabine (1 g/m, d1, d8) and cisplatin (25 mg/m d1-d3) on the tenth week. External beam radiotherapy was followed by image-guided brachytherapy of 24 Gy/ 4 fractions. Version 4 of the common terminology criteria for adverse events (CTCAE v 4.0) was used in grading the toxicities. Sixty-nine patients obtained complete response (CR), six had a partial response (PR), and five patients had stable disease (SD). The disease control rate (DCR= SD and ORR) and overall response rate (ORR= PR, CR or PR) were 92.6% and 85.2% respectively. The 3-year and 5-year estimated overall survival (OS) was 75.4% and 66.3%, and the 3-year and 5-year estimated progression-free survival (PFS) were 78.2% and 65.4%. The median PFS time and OS time were 36.8 months and 45.5 months, respectively. Distance metastasis was evident in the lung (3 patients), pelvic wall (2 patients), liver (3 patients) and bone (2 patients). Six (6) had a local relapse, and two (2) patients had local relapse plus simultaneous systemic metastatic tumour. Unlike past results, gemcitabine and cisplatin appear to be tolerable, efficient and feasible when combined with conformal radiotherapy.
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http://dx.doi.org/10.7150/jca.40276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066008PMC
February 2020

Effects of Yeast Autolysate in the Practical Diet on the Growth Performance, Immune Response, and Disease Resistance of Pacific White Shrimp.

J Aquat Anim Health 2020 09 16;32(3):109-115. Epub 2020 Aug 16.

The Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture.

The present study was conducted to investigate the effects of supplementing the practical diet with yeast autolysate (YA) on the growth performance, immunity, and disease resistance of Pacific white shrimp Litopenaeus vannamei. Four isonitrogenous and isolipidic practical diets were formulated. The relatively high-fish-meal control diet contained 25% fish meal without YA supplementation (E1). The other control diet contained 20% fish meal without YA (E2). With the E2 diet as the basis, two additional experimental diets were created by further supplementation with 1% YA (E3) and 2% YA (E4). The shrimp (initial weight: 0.30 ± 0.02 g) were fed with the four experimental diets for 8 weeks and then challenged with Vibrio parahaemolyticus. The results indicated that there were no significant differences in survival rate (SR) or feed intake (FI) among these groups. The weight gain rate (WGR) of group E1 was not significantly different from that of groups E3 and E4. The feed conversion ratio (FCR) in group E4 was lower than that of group E2, and group E4 had the highest protein efficiency ratio (PER). The total hemocyte counts (THC) and lysozyme activities in group E3 and group E4 were significantly higher than those of the other groups. Group E3 had the highest respiratory burst (RB). After V. parahaemolyticus administration, group E3 and group E4 had significantly lower cumulative mortalities than group E1 did. In conclusion, the 20% fish meal diet without YA supplementation (E2) yielded a significantly lower growth rate than the 25% fish meal diet without YA supplementation (E1) did. Furthermore, the Pacific white shrimp that received dietary supplementation with 1% YA demonstrated improved growth rate, immune response, and resistance to the V. parahaemolyticus challenge compared with those that were fed the 20% fish meal diet without YA supplementation (E2).
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http://dx.doi.org/10.1002/aah.10095DOI Listing
September 2020

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-β induction in human cells.

J Gen Virol 2019 09 15;100(9):1273-1281. Epub 2019 Jul 15.

Key Laboratory of Animal Epidemiology, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-β induction than that of its predecessor PB2-292I. IFN-β attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-β. In the mouse model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.
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http://dx.doi.org/10.1099/jgv.0.001294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414430PMC
September 2019

The Impact of Fetal Anomalies on Contemporary Labor Patterns.

Am J Perinatol 2019 12 14;36(14):1423-1430. Epub 2019 Jun 14.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Objective: To compare labor patterns in pregnancies affected by fetal anomalies to low-risk singletons.

Study Design: Labor data from the Consortium on Safe Labor, a multicenter retrospective study from 19 U.S. hospitals, including 98,674 low-risk singletons compared with 6,343 pregnancies with fetal anomalies were analyzed. Repeated-measures analysis constructed mean labor curves by parity, gestational age, and presence of fetal anomaly in women who reached full dilation. Interval-censored regression analysis adjusted for covariables was used to determine the median traverse times for labor progression.

Results: Labor curves for all groups indicated slower labor progress for patients with fetal anomalies. The most significant trends in median traverse times were observed in the preterm nulliparous and term multiparous groups. The median traverse times from 4 cm to complete dilation in the preterm nulliparous control versus anomaly groups were 5.0 and 5.4 hours ( < 0.0001).

Conclusion: Labor proceeds at a slower rate in pregnancies affected by anomalies.
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http://dx.doi.org/10.1055/s-0039-1691765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539907PMC
December 2019

Sequence characterization and expression pattern analysis of six kinds of IL-17 family genes in the Asian swamp eel (Monopterus albus).

Fish Shellfish Immunol 2019 Jun 26;89:257-270. Epub 2019 Mar 26.

School of Animal Science, Yangtze University, Jingzhou, 434020, China; Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, China. Electronic address:

Interleukin-17 (IL-17) is an important cytokine that plays a critical role in the inflammatory response and host defense against extracellular pathogens. In the present study, six novel IL-17 family genes (MaIL-17) were identified by analyzing Asian swamp eel (Monopterus albus) genome. Sequence analysis revealed that the MaIL-17 family genes shared similar features, comprising a signal peptide, an IL-17 superfamily region, and four conserved cysteines. Phylogenetic analysis showed that the MaIL-17 genes were clustered together with their corresponding IL-17 genes from other species. The similarity and identity of all IL-17 family genes indicated that the MaIL-17 genes are conserved among teleosts, while Ma-IL-17D is more conserved than the other Ma-IL-17s. Except for MaIL-17A/F3 and MaIL-17D, all MaIL-17s shared the same genomic structure as the genes from other fish, namely three exons and two introns. The MaIL-17s showed conserved synteny among fish, and we found that the MaIL-17D locus has a more conserved syntenic relationship with the loci from other fish and humans. These results demonstrated that MaIL-17D and human IL-17D might have evolved from a common ancestral gene and subsequently diverged. The analysis of swamp eel reference genes revealed that EEF1A1 (encoding eukaryotic translation elongation factor 1 alpha 1) was an ideal reference gene for accurate real-time qRT-PCR normalization in the swamp eel. The MaIL-17 genes are widely distributed throughout tissues, suggesting that MaIL-17s carry out their biological functions in immune and non-immune tissues compartments. The transcript of Ma-IL17s exhibited different fold changes in head kidney cells in response to Aeromonas veronii phorbol 12-myristate 13-acetate (PMA) and polyinosinic:polycytidylic acid (poly I:C) challenge, showing that MaIL-17A/F1 has stronger antiviral activities compared with other MaIL-17 family genes, and that MaIL-17A/F3 and MaIL-17A/F2 possess stronger effects against extracellular pathogens compared with the others; however, MaIL-17C2 and MaIL-17D may play vital roles during pathogen infection. The differential immune responses of these genes to Aeromonas veronii, PMA and poly I:C implied distinct mechanisms of host defense against extracellular pathogens.
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http://dx.doi.org/10.1016/j.fsi.2019.03.050DOI Listing
June 2019

Parotidectomy by an endoscopic-assisted postauricular-groove approach.

Head Neck 2019 09 14;41(9):2851-2859. Epub 2019 Mar 14.

Department of Otorhinolaryngology-Head and Neck Surgery, Peking University First Hospital, Beijing, China.

Background: To investigate the feasibility of an endoscopic-assisted postauricular-groove approach parotidectomy and to evaluate the advantages and limitations of such an approach.

Methods: A total of 72 patients with parotid gland tumors underwent a parotidectomy procedure between January 2014 and January 2016. Of the aforementioned patients, 15 were treated by a postauricular-groove approach (group I), whereas the remaining 57 were treated by the Blair "S" incision (group II).

Results: Difference in visual analogue scale score for aesthetic outcome (0 vs 3) and median intraoperative blood loss (30 vs 50 mL) was statistically significant. Operation time and transient facial nerve paralysis were comparable. No recurrence of tumors was found in either group.

Conclusion: The endoscopic-assisted postauricular-groove approach for limited parotid tumor resection offers several advantages over the conventional "S" incision parotidectomy. In addition, it is arguably safer and results in a superior aesthetic outcome.
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http://dx.doi.org/10.1002/hed.25720DOI Listing
September 2019

cAMP binds to closed, inactivated, and open sea urchin HCN channels in a state-dependent manner.

J Gen Physiol 2019 02 12;151(2):200-213. Epub 2018 Dec 12.

Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA

Hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channels are nonselective cation channels that regulate electrical activity in the heart and brain. Previous studies of mouse HCN2 (mHCN2) channels have shown that cAMP binds preferentially to and stabilizes these channels in the open state-a simple but elegant implementation of ligand-dependent gating. Distinct from mammalian isoforms, the sea urchin (spHCN) channel exhibits strong voltage-dependent inactivation in the absence of cAMP. Here, using fluorescently labeled cAMP molecules as a marker for cAMP binding, we report that the inactivated spHCN channel displays reduced cAMP binding compared with the closed channel. The reduction in cAMP binding is a voltage-dependent process but proceeds at a much slower rate than the movement of the voltage sensor. A single point mutation in the last transmembrane domain near the channel's gate, F459L, abolishes inactivation and concurrently reverses the response to hyperpolarizing voltage steps from a decrease to an increase in cAMP binding. ZD7288, an open channel blocker that interacts with a region close to the activation/inactivation gate, dampens the reduction of cAMP binding to inactivated spHCN channels. In addition, compared with closed and "locked" closed channels, increased cAMP binding is observed in channels purposely locked in the open state upon hyperpolarization. Thus, the order of cAMP-binding affinity, measured by the fluorescence signal from labeled cAMP, ranges from high in the open state to intermediate in the closed state to low in the inactivated state. Our work on spHCN channels demonstrates intricate state-dependent communications between the gate and ligand-binding domain and provides new mechanistic insight into channel inactivation/desensitization.
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http://dx.doi.org/10.1085/jgp.201812019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363418PMC
February 2019

Molecular characterization and expression analysis of Asian swamp eel (Monopterus albus) CXC chemokine receptor (CXCR) 1a, CXCR1b, CXCR2, CXCR3a, CXCR3b, and CXCR4 after bacteria and poly I:C challenge.

Fish Shellfish Immunol 2019 Jan 23;84:572-586. Epub 2018 Oct 23.

Engineering Research Center of Ecology and Agricultural Use of Wetland (Ministry of Education), Yangtze University, Jingzhou, 434024, PR China; The Key Laboratory of Mariculture (Education Ministry of China), Ocean University of China, 5 Yushan Road, Qingdao, Shandong, 266003, PR China. Electronic address:

The CXC chemokine receptors (CXCRs) play critical roles in innate and adaptive immune systems. In this study, six Asian swamp eel (Monopterus albus) CXCRs (MaCXCR1-4) were identified and their molecular characterization and expression patterns were analyzed. The open reading frames (ORFs) of MaCXCR1a, MaCXCR1b, MaCXCR2, MaCXCR3a, MaCXCR3b, and MaCXCR4 were 1074 bp (base pairs), 1080 bp, 1125 bp, 1146 bp, 1083 bp, and 1140 bp, and encoded proteins of 357 aa (amino acids), 359 aa, 374 aa, 381 aa, 360 aa, and 379 aa, respectively. All these CXCRs have seven conserved transmembrane domains and four cysteines (with the exception of MaCXCR3b). Multiple sequence alignment revealed that the MaCXCRs possess a typical G-protein receptor family 1 signature and a DRY motif. There are also one to four potential N-glycosylation sites in the extracellular regions of the MaCXCRs, mainly distributed in the N-terminus and extracellular hydrophilic loop (ECL) 2 region. Phylogenetic analysis demonstrated that the MaCXCRs were clustered together with homologous proteins from other fish. Taken together with the amino acid identity and similarity analysis, these results suggested that the MaCXCRs are conserved with other homologous genes, in which CXCR4 is more conserved than CXCR1-3. The MaCXCRs loci showed conserved synteny among teleost fish, and we found that human CXCR1 shares a common ancestor with fish CXCR1a. MaCXCRs were constitutively expressed in a wide range of tissues (especially in immune-related tissues) with different expression levels, suggesting that the MaCXCRs have different roles in un-stimulated tissues, and may play vital roles under normal conditions. MaCXCRs showed different fold changes in the spleen after Aeromonas veronii and polyinosinic-polycytidylic acid (poly I:C) challenge, which suggested that MaCXCR1a and MaCXCR3a have longer antiviral activities compared with their antibacterial functions, and that MaCXCR1b possesses stronger antiviral than antibacterial activity. MaCXCR4 may play vital roles during bacterial and viral infection; however, MaCXCR2 has relatively small effect in antibacterial and antiviral responses. The differential responses of these genes to bacteria and poly I:C implied the differences in the mechanisms of defense against viruses and bacteria.
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http://dx.doi.org/10.1016/j.fsi.2018.10.055DOI Listing
January 2019

Sequence analysis and characterization of type I interferon and type II interferon from the critically endangered sturgeon species, A. dabryanus and A. sinensis.

Fish Shellfish Immunol 2019 Jan 15;84:390-403. Epub 2018 Oct 15.

Key Lab of Freshwater Biodiversity Conservation Ministry of Agriculture, Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, 430223, China. Electronic address:

In the present study, we identify three type I interferon (IFN) genes (Ad/AsIFNe1-3) and a type II IFN gene (Ad/AsIFNγ) from the Dabry's sturgeon (Acipenser dabryanus) and the Chinese sturgeon (Acipenser sinensis). Sequence analysis revealed that Ad/AsIFNe1-3 and Ad/AsIFNγ contain several conserved characteristics, including signal peptides, interferon alpha, beta, and delta (IFabd) domains, and N-glycosylation sites. Ad/AsIFNe1-3 belongs to the type I IFN group I subgroup, possessing two conserved cysteines residues (C1 and C3), and Ad/AsIFNγ contained a conserved nuclear localization sequence (NLS) motif. Ad/AsIFNe1-3 and Ad/AsIFNγ contain signature motifs indicative of their corresponding IFN group. The Ad/AsIFNe1-3 and Ad/AsIFNγ genes were found to consist of 5 exons/4 introns and 4 exons/3 introns, respectively. These IFNs were separated by four phase 0 introns (type I IFN) and three phase 0 introns (type II IFN). The sequences of IFNe1-3 and IFNγ from the Dabry's sturgeon and the Chinese sturgeon were closely aligned, suggested that these two species are closely related. Phylogenetic analysis revealed that Ad/AsIFNe1-3 and Ad/AsIFNγ clustered together with the corresponding homologous proteins from other fish species. AdIFNe1-3 were found to be high expressed in early embryonic development, suggesting that AdIFNe1-3 might indicate maternal transmission, while AdIFNγ may not mediate embryonic development. Tissue distribution analysis revealed that AdIFNe1-3 and AdIFNγ carry out biological functions in immune and non-immune tissues compartments. AdIFNe1-3 and AdIFNγ can be stimulated by polyinosinic-polycytidylic acid (poly I:C) and lipopolysaccharides (LPS). AdIFNe1-3 have stronger antiviral activity than AdIFNγ, and AdIFNγ has a stronger antibacterial activity than AdIFNe1-3. The differential responses of these genes to poly I:C and LPS suggest differences in the mechanisms of defense against viruses and bacteria.
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http://dx.doi.org/10.1016/j.fsi.2018.10.038DOI Listing
January 2019

Measuring the Impact of Nonignorable Missingness Using the R Package isni.

Comput Methods Programs Biomed 2018 Oct 4;164:207-220. Epub 2018 Jul 4.

Division of Epidemiology & Biostatistics (M/C 923), School of Public Health, University of Illinois at Chicago, 1603 West Taylor Street, Room 984, Chicago, 60612-4336, IL.

Background And Objective: The popular assumption of ignorability simplifies analyses with incomplete data, but if it is not satisfied, results may be incorrect. Therefore it is necessary to assess the sensitivity of empirical findings to this assumption. We have created a user-friendly and freely available software program to conduct such analyses.

Method: One can evaluate the dependence of inferences on the assumption of ignorability by measuring their sensitivity to its violation. One tool for such an analysis is the index of local sensitivity to nonignorability (ISNI), which evaluates the rate of change of parameter estimates to the assumed degree of nonignorability in the neighborhood of an ignorable model. Computation of ISNI avoids the need to estimate a nonignorable model or to posit a specific magnitude of nonignorability. Our new R package, named isni, implements ISNI analysis for some common data structures and corresponding statistical models.

Result: The isni package computes ISNI in the generalized linear model for independent data, and in the marginal multivariate Gaussian model and the linear mixed model for longitudinal/clustered data. It allows for arbitrary patterns of missingness caused by dropout and/or intermittent missingness. Examples illustrate its use and features.

Conclusions: The R package isni enables a systematic and efficient sensitivity analysis that informs evaluations of reliability and validity of empirical findings from incomplete data.
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http://dx.doi.org/10.1016/j.cmpb.2018.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345389PMC
October 2018

Singlet oxygen modification abolishes voltage-dependent inactivation of the sea urchin spHCN channel.

J Gen Physiol 2018 09 24;150(9):1273-1286. Epub 2018 Jul 24.

Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA

Photochemically or metabolically generated singlet oxygen (O) reacts broadly with macromolecules in the cell. Because of its short lifetime and working distance, O holds potential as an effective and precise nanoscale tool for basic research and clinical practice. Here we investigate the modification of the spHCN channel that results from photochemically and chemically generated O The spHCN channel shows strong voltage-dependent inactivation in the absence of cAMP. In the presence of photosensitizers, short laser pulses transform the gating properties of spHCN by abolishing inactivation and increasing the macroscopic current amplitude. Alanine replacement of a histidine residue near the activation gate within the channel's pore abolishes key modification effects. Application of a variety of chemicals including O scavengers and O generators supports the involvement of O and excludes other reactive oxygen species. This study provides new understanding about the photodynamic modification of ion channels by O at the molecular level.
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http://dx.doi.org/10.1085/jgp.201711961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122923PMC
September 2018

Analysis of the expression patterns of the cytokine receptor family B (CRFB) and interferon gamma receptor (IFNGR) in Dabry's sturgeon (Acipenser dabryanus).

Dev Comp Immunol 2018 07 16;84:420-426. Epub 2018 Mar 16.

School of Animal Science, Yangtze University, Jingzhou, 434020, China; The Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture), The Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, Qingdao, China. Electronic address:

Teleost fish have more complex interferon receptor systems than mammals. In the present study, genes encoding four cytokine receptor family B (CRFBs) and two interferon gamma receptors (IFNGRs) in Dabry's sturgeon (Acipenser dabryanus) were identified by RNA-sequencing. Sequence analysis revealed that the Dabry's sturgeon CRFBs and IFNGRs contained several conserved characteristics features, including signal peptides and a transmembrane domain. Phylogenetic analysis suggested that they belong to the CRFB3, CRFB5, and IFNGR protein families, and were named CRFB3a, CRFB3b, CRFB5a, CRFB5b, IFNGR1, and IFNGR2. The expression patterns of the CRFB and IFNGR genes were investigated in Dabry's sturgeon. The expression levels of CRFB5a, CRFB5b, and IFNGR1 showed no significant changes, suggesting that those genes do not mediate embryonic development. By contrast, the high expression levels of CRFB3a, CRFB3b, and IFNGR2 in the fertilized egg, 16-cell phase, and initial blastula stage implied the existence of maternally expression in the oocyte and association with embryonic development. Tissue distribution analysis revealed that the CRFB and IFNGR proteins have potential functions in immune and non-immune tissue compartments. Comprehensive analysis in Dabry's sturgeon revealed that the expression fold changes of CRFB3a, CRFB3b, CRFB5a, and CRFB5b in Dabry's sturgeon stimulated with poly I:C were higher than those in fish administrated with lipopolysaccharide (LPS). Conversely, the fold changes IFNGRs mRNA levels stimulated with LPS were higher than those in fish administrated with poly I: C. CRFB5a and IFNGR2 genes showed the earliest responses to the poly I: C, and the CRFB5a and IFNGR1 genes showed the earliest responses to LPS. These results implied that CRFB5a has important role in the IFN immune response. Our findings indicated that the Dabry's sturgeon CRFB and IFNGR genes have important functions in antiviral and antibacterial immune responses. The differential responses of these genes to poly I: C and LPS implied differences in the defense mechanisms against viruses and bacteria.
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http://dx.doi.org/10.1016/j.dci.2018.03.011DOI Listing
July 2018

Reduced glutathione supplementation in practical diet improves the growth, anti-oxidative capacity, disease resistance and gut morphology of shrimp Litopenaeus vannamei.

Fish Shellfish Immunol 2018 Feb 26;73:152-157. Epub 2017 Nov 26.

The Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China.

The present study was conducted to investigate the effects of reduced glutathione (GSH) supplementation in practical diet on growth performance, anti-oxidative response, disease resistance and intestine morphology of shrimp Litopenaeus vannamei. Two control diets based on the commercial formulation were designed with high level (27%) and low level (22%) of fish meal, respectively. Based on the control diet with low level of fish meal, 75, 150 and 225 mg/kg of GSH were added, respectively, to make the other three experimental diets. The five formulated diets were named as C1, C2, G1, G2 and G3, respectively. The shrimp (initial body weight: 0.30 ± 0.02 g) were fed with the five experimental diets for 8 weeks followed by a challenge test with Vibrio parahaemolyticus. The results showed that the specific growth rate (SGR) of shrimp in the C2 group was significantly lower than that in C1. The SGRs in G1 and G2 had no significant difference with those in C1 and C2. However, the SGR in G3 was significantly lower than that in C1. The serum GSH concentration in C2 was significantly lower than the other groups, but the malondialdehyde concentration was significantly higher. The supplementation of dietary GSH significantly improved the total anti-oxidative capacity and activities of glutathione S-transferase and glutathione peroxidase in serum. The villus height of intestine in the GSH supplemented groups had no significant difference with C1, but was significantly higher than C2. The jejunum wall thickness of intestine in G2 and G3 was significantly higher than those in the other groups. After the challenge test, the cumulative mortalities in G1 and G2 were significantly lower than C1 and C2. However, there was no significant difference in cumulative mortalities among G3, C1 and C2. In conclusion, based on the present experimental conditions, 75-150 mg/kg of GSH was suggested to be supplemented into the practical diet to improve the growth, anti-oxidative capacity, disease resistance and gut health of shrimp L. vannamei.
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http://dx.doi.org/10.1016/j.fsi.2017.11.043DOI Listing
February 2018

Functional characterization of interferon regulatory factor 5 and its role in the innate antiviral immune response.

Fish Shellfish Immunol 2018 Jan 5;72:31-36. Epub 2017 Dec 5.

Engineering Research Center of Ecology and Agricultural Use of Wetland, Ministry of Education, Jingzhou 434020, China; School of Animal Science, Yangtze University, Jingzhou 434020, China. Electronic address:

In mammals, type I interferons (IFNs) are primarily regulated by transcription factors of the IFN regulatory (IRF) family. Interferon regulatory factor 5 (IRF-5) plays pivotal roles in antiviral and inflammatory responses. In the present study, we found that zebrafish (Danio rerio) IRF5 is a key player in the regulation of the expression of type I IFN and its antiviral immune response. IRF5 was upregulated in zebrafish embryonic fibroblast cells (ZF4) when challenged with grass carp reovirus (GCRV). Moreover, the expression profiles of Mx, IFN, Viperin, and IRF7, but not IRF3, were upregulated by overexpression of IRF5 in Epithelioma papulosum cyprinid cells (EPCs). Luciferase assays revealed that the activation of the IFNϕ1 promoter was stimulated by overexpression of IRF5 and IRF5-△IAD (IRF5 lacking the IRF-associated domain), respectively. However, overexpression of IRF5 or IRF5-△IAD inhibited the activity of the IFNϕ3 promoter. IRF5-△DBD (lacking the DNA-binding domain) had no influence in the activation of the IFNϕ1 and IFNϕ3 promoters. Furthermore, the determination of the cytopathic effect (CPE) numbers and viral titers revealed that the viral concentration was reduced by ectopic expression of IRF5 in EPC cells. Ectopic expression of IRF5 in EPC cells could protect cells from GCRV and significantly inhibited GCRV virus replication. These data indicated that IRF5 could limit viral replication through an IFN-dependent pathway.
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http://dx.doi.org/10.1016/j.fsi.2017.10.042DOI Listing
January 2018

Identification and Functional Validation of Autolysis-Associated Genes in ATCC BAA-365.

Front Microbiol 2017 19;8:1367. Epub 2017 Jul 19.

Key Laboratory of Agro-Food Processing and Quality Control, Institute of Agro-Food Science and Technology, Chinese Academy of Agricultural ScienceBeijing, China.

Lactic acid bacteria (LAB) are important organisms in food production. Indeed, LAB autolysis is very critical in dairy processing. For example, it influences the development of cheese flavor by releasing intracellular enzymes, and controls cell growth in yogurts and probiotic products. Two component systems (TCS) constitute essential environmental sensors and effectors of signal transduction in most bacteria. In the present work, mutants of one TCS (LBUL_RS00115/LBUL_RS00110) were generated to assess the relationship between TCS and cell autolysis. The mutants displayed decreased autolysis in comparison with wild type; meanwhile, complementation reversed this effect. The interaction between LBUL_RS00115 and LBUL_RS00110 was confirmed by yeast two-hybrid analysis. These observations suggested that the TCS (LBUL_RS00115/LBUL_RS00110) was involved in autolysis in subsp. .
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http://dx.doi.org/10.3389/fmicb.2017.01367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516001PMC
July 2017

Enhanced pathogenicity and neurotropism of mouse-adapted H10N7 influenza virus are mediated by novel PB2 and NA mutations.

J Gen Virol 2017 Jun 8;98(6):1185-1195. Epub 2017 Jun 8.

Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine and State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, PR China.

The H10 subtype of avian influenza viruses (AIVs) circulates globally in wild birds and poultry, and this subtype has been shown to be increasingly prevalent in China. Among the various H10 viruses, H10N7 AIVs have caused repeated mammal and human infections. To investigate their genetic adaptation in mammals, we generated a mouse-adapted avian H10N7 variant (A/mallard/Beijing/27/2011-MA; BJ27-MA) which exhibited increased virulence in mice compared to wild-type virus and acquired neurotropism. Sequencing showed the absence of the widely recognized mammalian adaptation markers of E627K and D701N in PB2 in the mouse-adapted strain; instead, five amino acid mutations were identified: E158G and M631L in PB2; G218E in haemagglutinin (H3 numbering); and K110E and S453I in neuraminidase (NA). The neurovirulence of the BJ27-MA virus necessitated the combined presence of the PB2 and NA mutations. Mutations M631L and E158G of PB2 and K110E of NA were required to mediate increased virus replication and severity of infection in mice and mammalian cells. PB2-M631L was functionally the most dominant mutation in that it strongly upregulated viral polymerase activity and played a critical role in the enhancement of virus replication and disease severity in mice. K110E mutation in NA, on the other hand, significantly promoted NA enzymatic activity. These results indicate that the novel mutations in PB2 and NA genes are critical for the adaptation of H10N7 AIV in mice, and they could serve as molecular signatures of virus transmission to mammalian hosts, including humans.
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http://dx.doi.org/10.1099/jgv.0.000770DOI Listing
June 2017

Bioinformatics and expression analysis of finTRIM genes in grass carp, Ctenopharyngodon idella.

Fish Shellfish Immunol 2017 Jul 2;66:217-223. Epub 2017 May 2.

Engineering Research Centre of Ecology and Agricultural Use of Wetland, Ministry of Education, Jingzhou 434020, China; School of Animal Science, Yangtze University, Jingzhou 434020, China. Electronic address:

The tripartite motifs (TRIMs) constitute a large family of proteins containing a Really Interesting New Gene (RING) domain, a B-box domain and coiled-coil region followed by different C-terminal domains. TRIM proteins play multiple roles in various cellular processes, including cell growth, differentiation, apoptosis and antiviral immunity. Fish novel large multigene TRIM genes (finTRIM/ftr) appear only in teleosts and play a vital role in antiviral responses. Phylogenetic analysis revealed the existence of different subsets of novel fish TRIM 14 genes (finTRIM14/ftr14), ftr51, ftr67, ftr72, ftr82, ftr83, and ftr99 in grass carp (Ctenopharyngodon idella), suggesting lineage-specific diversification events. Therefore, the number of finTRIM genes varies greatly among species. The ftr genes in grass carp, which are closely related to zebrafish and possess various evolutionary branches, have evolved faster than human TRIMs. The predicted protein domains were almost identical RING zinc finger domains, with the exception of ftr72, the B-box domain (excluding ftr67, ftr82, ftr83), and the B30.2 domain, which evolved under positive selection (with the exception of ftr67, and ftr72). The genes were predominantly expressed in the spleen, gill and head kidney. These findings indicate that the ftr genes in grass carp are involved diverse cellular processes, including innate immune responses.
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http://dx.doi.org/10.1016/j.fsi.2017.05.004DOI Listing
July 2017

Analysis of the expression patterns of the novel large multigene TRIM gene family (finTRIM) in zebrafish.

Fish Shellfish Immunol 2017 Jul 28;66:224-230. Epub 2017 Apr 28.

Engineering Research Centre of Ecology and Agricultural Use of Wetland, Ministry of Education, Jingzhou 434020, China; School of Animal Science, Yangtze University, Jingzhou 434020, China. Electronic address:

Tripartite motif (TRIM) proteins are receiving increased research interest because of their roles in a wide range of cellular biological processes in innate immunity. In zebrafish (Danio rerio), the functions of the finTRIM (ftr) family are unclear. In the present study, we investigated the expression pattern of ftr12, ftr51, ftr67, ftr82, ftr83, and ftr84 in zebrafish for the first time. The results showed that ftr12, ftr67, and ftr84 are maternally expressed in the oocyte and highly expressed at the early stage (0-4 hpf) of embryo (P < 0.05), suggesting their involvement in the embryonic innate defense system. The ftr82 gene was highly expressed at 8 hpf (P < 0.05), which implied that the embryos could synthesize their own immunity-related mRNAs. However, ftr51 and ftr83 were highest at 8 hpf (2.33 and 51.53 relative to β-actin respectively) and might mediate embryonic development. The expression levels of ftr12, ftr51, and ftr67 were highest in the gill, intestines, and liver, respectively. Ftr82, ftr83, and ftr84 were predominantly expressed in the kidney, suggesting that these finTRIMs might play roles in both immunity and non-immunity-related tissue compartments. Zebrafish embryonic fibroblast (ZF4) cells were infected with Grass carp reovirus (GCRV) and Spring viremia of carp virus (SVCV). During GCRV infection, the expression of ftr12 was significantly upregulated from 12 h to 24 h; and ftr51 and ftr67 increased from 3 h to 12 h. The expressions of ftr82, ftr83, and ftr84 were only upregulated at 12 h, 12 h, and 24 h, respectively. All of these genes were significantly downregulated at 48 h (P < 0.05). Challenge with SVCV upregulated the expressions of ftr12 and ftr51 at 12 h and 48 h (P < 0.05), respectively, and ftr67 reached its highest expression level at 3 h. ftr82 showed only a slight upregulation at 6 h and 48 h, and ftr83 and ftr84 were consecutively increased, reaching their highest levels at 12 h (P < 0.05). Meanwhile, ftr67 and ftr83 were significantly downregulated at 48 h (P < 0.05). Our research demonstrated that ftr12, ftr51, ftr67, ftr82, ftr83, and ftr84 probably have important roles in innate immune responses and in non-immunity-related tissues.
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http://dx.doi.org/10.1016/j.fsi.2017.04.024DOI Listing
July 2017

The regulation effects of danofloxacin on pig immune stress induced by LPS.

Res Vet Sci 2017 Feb 6;110:65-71. Epub 2016 Nov 6.

College of Animal Science, Yangtze University, Jingzhou, Hubei 434025, China. Electronic address:

Danofloxacin (DAN) is one of the Fluoroquinolone drugs (FQs) that has been widely used in the control and prevention of bacterial infectious disease in animal production. Most of the FQs have an obvious protective effect against lipopolysaccharide (LPS) induced Immune stress. However, the effect of DAN on the host immune system of animals remains unknown. In this study, a fever piglet model was built and a systematic survey of the response of inflammatory genes and mediators to DAN treatment and LPS induction was performed in the pig. The results indicated that the IL-1β, TNF-α, IL-6, NO (nitric oxide), and PGE2 (prostaglandin E2) levels were significantly suppressed in plasma and porcine alveolar macrophage 3D4/2 cells compared with the LPS treatment group. Interestingly, the IL-10 production was further stimulated by DAN treatment in the LPS challenged piglet. Our results suggested that DAN could relieve acute inflammation through inhibiting the activation of inflammatory genes introduced by LPS.
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http://dx.doi.org/10.1016/j.rvsc.2016.11.005DOI Listing
February 2017